The 1-aryl-1-hydroxy-2-methylaminopropanes are optically active compounds which are pharmaceutically useful. Unfortunately, one stereo isomer is generally the active component while the other isomer is either inert, less effective or deactivating.
One of the most important 1-aryl-1-hydroxy-2-methylaminopropane is d-pseudoephedrine. It has been heretofore prepared by several methods from 1-ephedrine. For example, treatment of 1-ephedrine with aqueous HCl gave a diasteriomeric mixture of approximately 40 percent 1-ephedrine and 60 percent d-pseudoephedrine after rather long reaction times (e.g. 40 hours) and elevated temperatures. Separation of such optical isomers is tedious, time consuming, and has heretofore proceeded in rather low yields. Emde, Helv. Chem. Acta., 12, 377 (1929).
In yet another process, 1-ephedrine was converted to its monoacetate (amide) and hydrolyzed to give again a diasteriomeric mixture of approximately 35 percent 1-ephedrine and approximately 65 percent d-pseudoephedrine. Welsh, J. Am. Chem. Soc., 69, 128 (1947).
It has also been reported that the reaction of 1-ephedrine hydrochloride with 10 moles excess acetic anhydride gave d-pseudoephedrine hydrochloride. No yields were reported. Schmidt and Calliess, Arch. Pharm., 250, 154 (1912).
It was also reported that the reaction of 1-ephedrine with o-methylbenzoyl chloride and subsequent hydrolysis of the resulting amide gave d-pseudoephedrine. Welsh, J. Am. Chem. Soc., 71, 3500 (1949).